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A selective HK2 degrader suppresses SW480 cancer cell growth by degrading HK2

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Chinese Chemical Letters 2024年第8期35卷 201-204页

作者： yang Liu yan Liu Kaiyin yang zhiruo Zhang Wenbo Zhang Bingyou yang Hua Li Lixia Chen Wuya College of Innovation Key Laboratory of Structure-Based Drug Design&DiscoveryMinistry of EducationShenyang Pharmaceutical UniversityShenyang 110016China Key Laboratory of Basic and Application Research of Beiyao Ministry of EducationHeilongjiang University of Chinese MedicineHarbin 150006China Institute of Structural Pharmacology&TCM Chemical Biology College of PharmacyFujian University of Traditional Chinese MedicineFuzhou 350122China Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation School of PharmacyTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

Hexokinase 2(HK2)is the rate-limiting enzyme in the first step of glycolysis,catalyzing glucose to glucose-6-phosphate,and overexpressed in most cancer ***2 also binds to voltage-dependent anion channel(VDAC)to stabilize the mitochondrial outer membrane,which inhibits cancer cell ***,HK2 has become a potential target for cancer *** targeting chimeras(PROTACs)are hetero-bifunctional molecules that recruit an E3 ubiquitin ligase to a given substrate protein resulting in its targeted *** potent and specific PROTACs targeting dissimilar targets have been *** this study,an HK2 PROTAC,4H-5P-M,was developed and induced the degradation of HK2 relying on the ubiquitin-proteasome *** was found that 4H-5P-M as an effective HK2 degrader induced HK2 degradation in a dose-and time-dependent manner and suppressed the growth of SW480 cells.4H-5P-M selectively induced HK2 degradation at a lower concentration than other hexokinase ***,it could suppress glycolysis and accelerate the apoptosis of cancer ***,it provided a new insight into the development of anti-tumor drugs.

关键词： HK2 PROTACs Degrader Anti-tumor SW480

A review:the mechanism of plant-derived polysaccharides on osteoblasts and osteoclasts

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未来食品学报(英文) 2024年第3期4卷 183-192页

作者： Mengjie Ren Adel F.Ahmed Meng Li Menghan Li zhiruo.yan Jinmei Wang National R&D Center for Edible Fungus Processing Technology Henan UniversityKaifeng 475004China Joint International Research Laboratory of Food&Medicine Resource Function Henan ProvinceKaifeng 475004China Medicinal and Aromatic Plants Researches Department Horticulture Research InstituteAgricultural Research CenterGiza 12511Egypt

Bone loss and deterioration of bone microarchitecture would increase the bone fragility and fracture risk,leading to the *** and more evidences proved that plant-derived polysaccharides could have a remarkable influence on osteoblasts and osteoclasts,exerting anti-osteoporosis *** to the previous research,the extract of Cibotium barumoz,Achyranthes bidentata,Curculigo orchioides,Epimedium brevicornum,Angelica sinensis,Polygonatum sibiricum,Dendrobium officinale,Morinda officinalis,Nelumbo mucifera,Diospyros kaki,Hordeum vulgare,Cistanche deserticola,Commiphora Myrrha and other plant-derived polysaccharides could benefit to the osteoblasts and *** essential mechanisms are mainly related to the activation or inhibition of many factors,including runt-related transcription factor 2(Runx2),B-catenin,osterix(Osx),activator protein-1(AP-1),osteocalcin(OCN/BGP),alkaline phosphatase(ALP),osteopontin(OPN),bone morphogenetic protein(BMP),phosphatidylinositol 3-kinase(PI3K)/C-Jun N-terminal kinase(JNK)/extracellular regulated protein kinase(ERK),osteoprotegerin(OPG),receptor activator of nuclear factor-kB(RANK),monocyte/macrophage colony-stimulating factor(M-CSF),tumor necrosis factor receptor-associated factor 6(TRAF-6),receptor activator of nuclear factor(NF)-KB ligand(RANKL),nuclear factor of activated T cells 1(NFATc1),c-Fos,matrix metallopeptidase-9(MMP-9),glycogen synthase kinase 3β(GSK3B)/B-catenin,nuclear factor E2-related factor 2(Nf2),as well as these related pathways,such as Wnt/p-catenin,BMP-2/SMAD1/5/8,PI3K/AKT,OPG/RANKL/RANK,NF-κB,MAPKs,*** plant-derived polysaccharides could improve the dynamic balance of bone formation and resorption through promoting the differentiation and maturation of osteoblast or inhibiting its *** reviewed plant-derived polysaccharides and their regulating mechanisms on the osteoclasts and osteoblasts provide the evidences for the development of osteoporosis therapeutics.

关键词： Osteoporosis Plant-derived polysaccharides Osteogenesis promotion Osteoclasts inhibition

Comprehensive transcriptional atlas of human adenomyosis deciphered by the integration of single-cell RNA-sequencing and spatial transcriptomics

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Protein & Cell 2024年第7期15卷 530-546页

作者： Tao Chen Yiliang Xu Xiaocui Xu Jianzhang Wang zhiruo Qiu Yayuan Yu Xiaohong Jiang Wanqi Shao Dandan Bai Mingzhu Wang Shuyan Mei Tao Cheng Li Wu Shaorong Gao Xuan Che Department of Obstetrics and Gynecology Affiliated Women and Children Hospital of Jiaxing UniversityJiaxing 314000China Shanghai Key Laboratory of Maternal Fetal Medicine Clinical and Translational Research Center of Shanghai First Maternity and Infant HospitalFrontier Science Center for Stem Cell ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China Key Laboratory of Animal Bioengineering and Disease Prevention of Shandong Province College of Animal Science and TechnologyShandong Agricultural UniversityTaian 271018China Women’s Hospital School of MedicineZhejiang UniversityHangzhou 310013China Postgraduate training base Alliance of Wenzhou Medical University Wenzhou Medical UniversityWenzhou 325035China Jiaxing University Master Degree Cultivation Base Zhejiang Chinese Medical UniversityHangzhou 310053China Shanghai Key Laboratory of Maternal Fetal Medicine Shanghai Institute of Maternal-Fetal Medicine and Gynecologic OncologyClinical and Translational Research CenterShanghai First Maternity and Infant HospitalSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China

Adenomyosis is a poorly understood gynecological disorder lacking effective *** persists regarding“invagination”and“metaplasia”*** endometrial-myometrial junction(EMJ)connects the endometrium and myometrium and is important for diagnosing and classifying adenomyosis,but its in-depth study is just *** single-cell RNA sequencing and spatial profiling,we mapped transcriptional alterations across eutopic endometrium,lesions,and *** lesions,we identified unique epithelial(LGR5+)and invasive stromal(PKIB+)subpopulations,along with WFDC1+progenitor cells,supporting a complex interplay between“invagination”and“metaplasia”theories of ***,we observed endothelial cell heterogeneity and abnormal angiogenic signaling involving vascular endothelial growth factor and angiopoietin ***-cell communication differed markedly between ectopic and eutopic endometrium,with aberrant signaling in lesions involving pleiotrophin,TWEAK,and WNT *** study reveals unique stem cell-like and invasive cell subpopulations within adenomyosis lesions identified,dysfunctional signaling,and EMJ abnormalities critical to developing precise diagnostic and therapeutic strategies.

关键词： adenomyosis single-cell RNA sequencing spatial transcriptomics endometrial-myometrial junction progenitor cells

Towards Data-Driving Multi-View Evaluation Framework for Scratch

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Tsinghua Science and Technology 2024年第2期29卷 517-528页

作者： Xiaolin Chai yan Sun yan Gao Department of Computer Science Beijing University of Posts and TelecommunicationBeijing 100876China Intellectual Property Institute Shandong Polytechnic CollegeJining 272067China

As one of the most popular visual programming languages,Scratch has a lot of evaluation around *** evaluation can help programmers understand their projects *** the same time,it can also provide a reference for them to browse other projects in the online *** of the existing evaluations on Scratch are carried from three perspectives:Computational Thinking(CT)ability,visual presentation aesthetics,and code *** them,the assessment of CT and code quality is mainly carried out from the program script,while the evaluation of visual aesthetics is analyzed from the perspective of image sequences generated by project *** single-view evaluation focuses on the performance of a program in a certain aspect and is *** this paper,we propose a multi-view evaluation framework to integrate various evaluations using different *** quantitatively analyze the assessment of different views driven by *** with overall evaluations that represent human opinions,we analyze their differences and *** experiments,we determine the weights of different integration policies,the proposed multi-view evaluation method can generate evaluation results similar to human opinions.

关键词： Scratch Computational Thinking(CT) visual aesthetic static analysis integration policy machine learning

Forward to the Special Topic on“Solving Differential Equations with Deep Learning”

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Journal of Systems Science & Complexity 2024年第2期37卷 389-390页

作者： yan Zhenya Academy of Mathematics and Systems Science Chinese Academy of SciencesBeijing 100190China

The concept of artificial intelligence(AI)was first presented at the Dartmouth SummerResearch Project on AI hosted by McCarthy and Minsky in *** that,the developmentof AI has experienced ups and downs due to some limited conditions including intelligentcomputing techniques,computer and hardware and software^([1,2]).In particular,with the rapidof deep artificial neural networks,machine learning(ML)and deep learning(DL)techniques^([3,4])have been applied in many fields of science and engineering,including machine translation,image recognition,genomics,scientific computing and atmospheric science,etc^([5]).

关键词： has artificial hardware

Large eddy simulation study of 3D wind field in a complex mountainous area under different boundary conditions

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Journal of Zhejiang University-Science A(Applied Physics & Engineering) 2024年第7期25卷 541-556页

作者： yan LI Lei yan Xuhui HE School of Civil Engineering Central South UniversityChangsha410075China National Engineering Research Center for High-speed Railway Construction Changsha410075China Hunan Provincial Key Laboratory for Disaster Prevention and Mitigation of Rail Transit Engineering Structures Changsha410075China

Large eddy simulations generally are used to predict 3D wind field characteristics in complex mountainous *** simulation boundary conditions,such as the height and length of the computational domain or the characteristics of inflow turbulence,can significantly impact the quality of *** this study,we examined these boundary conditions within the context of the mountainous terrain around a long-span cable-stayed bridge using a wind tunnel *** sizes of computational domains and turbulent incoming wind velocities were used in large eddy *** results show that when the height of the computational domain is five times greater than the height of the terrain model,there is minimal influence from the top wall on the wind field characteristics in this complex mountainous *** the length of the wake region of the computational domain has negligible effects on the wind *** in the inlet boundary reduces the length of the wake region on a leeward hill with a low slope,but has less impact on the mean wind velocity of steep hills.

关键词： Large eddy simulation(LES) Spectral representation method Recycling method High mountainous canyon Wind characteristics Atmospheric boundary layer Computational domain

Application of carbon materials for Zn anode protection in aqueous Zn metal batteries

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Rare Metals 2024年第10期43卷 4807-4843页

作者： Cui-Qin Chao yan-Nan Li yan Zhao College of Energy Materials and Chemistry Inner Mongolia University School of Physical Science and Technology Inner Mongolia University

Aqueous Zn metal batteries (AZMBs) have gained widespread attention due to their high theoretica specific capacity,good safety,and low *** Zn anodes suffer from serious problems of dendrites and side reactions,which should be solved by modifying the Zn anode (Zn host,protective layer),electrolyte,and *** materials with structurally tunable and physicochemical stability properties have been widely used in the study of Zn anode protection and have also been reviewed in the past ***,review reports on carbon-based Zn anodes for Zn anode protection from new perspectives are still urgently ***,the timeliness of the review reports is very valuable for researchers to timely and accurately understand the dynamics of the research ***,this review firs reports the significance of AZMBs and summarizes the current main challenges that should be solved for practical ***,the ways to construct long-life Zn anodes using carbon materials from the perspectives of modified carbon materials with gradient properties (gradient zincophilicity,gradient electrical conductivity,and multigradient deposition) as protective layers/hosts to guide Zn ions toward bottom-up gradient Zn deposition are *** addition,the recent advances of carbon materials for electrolyte and separator modifications are ***,the remaining challenges and future perspectives of carbon materials in AZMBs Zn anode protection are briefly outlined.

关键词： Anode protection Aqueous Zn battery Carbon Gradient deposition

Electromagnetic characteristic analysis and design of a linear motor used for ultra-high-speed EMS maglev train

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Science China(Technological Sciences) 2024年第6期67卷 1957-1973页

作者： GAO Han SHI TingNa GAO XinMai LEI yanXiao yan Dong GUO Liyan yan yan College of Electrical Engineering Zhejiang UniversityHangzhou310027China Zhejiang University Advanced Electrical Equipment Innovation Center Hangzhou311107China State Key Laboratory of High-speed Maglev Transportation Technology Qingdao266100China CRRC Qingdao Sifang Co.Ltd. Qingdao266111China

The operating speed of the commercial electromagnetic suspension(EMS)maglev train has been over 430 km/h,making it the fastest means of land *** the increasing demands of people traveling,it is necessary to further improve the operating speed of maglev *** to examine whether the existing EMS system can meet the requirements of ultra-highspeed operation(more than 600 km/h),the electromagnetic characteristics of an EMS linear motor under the operating speed of 600–1000 km/h fed by a square-wave voltage supply is investigated in this ***,an electromagnetic field model of the EMS system under the square-wave voltage supply is established to investigate its electromagnetic performance,e.g.,the characteristics of phase current,the magnetic flux density,and the electromagnetic ***,the relationship between the harmonic components of the air-gap magnetic flux density and electromagnetic force is investigated using the two-dimensional fast Fourier transform(2D-FFT)to reveal the mechanism of electromagnetic force ***,to address the issues of excessive armature current density and significant electromagnetic force ripple,the linear motor is re-designed by enlarging the stator slot area and reshaping the mover's main magnetic ***,the Taguchi method is used to further improve the electromagnetic characteristics of the linear electric ***,the effectiveness of the proposed optimal design is validated by the finite-element analysis(FEA)based co-simulation.

关键词： ultra-high-speed maglev transportation electromagnetic suspension(EMS) linear motor electromagnetic force ripple suppression

Thermal and mechanical behavior of casting copper alloy wheel during wheel and belt continuous casting process

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China Foundry 2024年第1期21卷 82-90页

作者： Kun Gao yan Peng School of Mechanical Engineering Yanshan UniversityQinhuangdao 066004HebeiChina

To investigate the thermal and mechanical behavior of casting wheel,a two-dimensional thermoelastic-plastic finite element model was used to predict the temperature,stress and distortion distribution of the casting wheel during the wheel and belt continuous casting *** effects of grinding thickness and casting speed on the thermal and mechanical behaviors of the center of the hot face of the casting wheel were discussed in *** each rotation,the casting wheel passes through four different spray *** results show that the temperature distribution of the casting wheel in different spray zones is similar,the temperature of the hot face is the highest and the temperature reaches the peak in the spray zoneⅢ.The stress and distortion depend on the temperature distribution,and the maximum stress and distortion of the hot face are 358.2 MPa and 1.82 mm,*** temperature at the center of the hot face decreases with increasing grinding thickness and increases with increasing casting speed.

关键词： casting wheel finite element model grinding thickness casting speed hot face spray zones